Portable electrotherapy device for treating osteoarthritis and other diseases, defects and injuries of the knee joint

ABSTRACT

A portable device for applying therapeutic electrical signals and/or electromagnetic fields to a patient&#39;s knee for the treatment of osteoarthritis and other diseases, defects and injuries. The device is operable in several modes to deliver signals to the patients knee so as to cause an electric and/or electromagnetic field to be generated that selectively up-regulates gene expression of Aggrecan and Type II Collagen while simultaneously selectively down-regulating the gene expression of metalloproteases. The device includes a signal generator that generates compound electric signals including a 60 kHz sine wave having a peak to peak voltage of approximately 4.6 V to 7.6 V and a 100% duty cycle signal that is generated for approximately 30 minutes and a 50% duty cycle signal that is generated for approximately 1 hour after the 100% duty cycle signal. These compound electric signals are communicated to electrodes or coils in the proximity of a patient&#39;s knee for the generation of a specific and selective electromagnetic field that treats the diseased tissue.

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS

The present application is a Continuation-in-Part of currently pendingU.S. patent application Ser. No. 10/257,126, filed Oct. 8, 2002,entitled “Regulation of Genes Via Application of Specific and SelectiveElectrical and Electromagnetic Signals”, and is related to U.S. patentapplication Ser. No. 10/255,241, filed Sep. 26, 2002, entitled“Regulation of Aggrecan Gene Expression with a Specific and SelectiveElectrical Signal”, Ser. No. 10/267,708, filed Oct. 9, 2002, entitled“Regulation of Type II Collagen Gene Expression with a Specific andSelective Electrical Signal”, and Ser. No. ______, filed Jun. 9, 2003,entitled “Method and Apparatus for Treating Osteoarthritis, CartilageDisease, Defects and Injuries in the Human Knee Joint.” The contents ofthese applications are hereby incorporated by reference.

FIELD OF THE INVENTION

The present invention is directed to a device and a method of designinga device that will deliver specific and selective electrical andelectromagnetic signals to diseased articular cartilage for thetreatment of osteoarthritis, cartilage disease, defects and injuries inthe knee joint.

DESCRIPTION OF THE PRIOR ART

The present inventor has disclosed in the above-mentioned relatedapplications methods and devices for specifically and selectivelyup-regulating gene expression of aggrecan (increase in aggrecan mRNA)and Type II collagen (increase in Type II collagen mRNA) anddown-regulating gene expression of metalloproteases (decrease in MMP-I,MMP-3 and MMP-13) by applying specific and selective electrical andelectromagnetic signals to the knee joint in patients afflicted withosteoarthritis, cartilage disease, defects and injuries. As described inthese patent applications, specific and selective capacitively coupledelectric fields of 10-20 mV/cm amplitude at a frequency of 60 kHz and asine wave configuration showed achieved maximum up-regulation ofaggrecan mRNA when the electric signal was applied for 1 hour at a 50%duty cycle, maximum up-regulation of Type II collagen mRNA when theelectric signal was applied for 30 minutes at a 8.3% duty cycle, andmaximum down-regulation of MMP-I when the electric signal was applied ata duty cycle of 100% for 30 minutes. It is desired to develop a devicethat is specifically designed to selectively generate such signals forup-regulating the expression of various genes (for example aggrecanmRNA, Type II collagen mRNA) with specific and selected signals andalso-down-regulating the expression of other genes (for example, MMP-1,MMP-3, MMP-4) in the treatment of osteoarthritis, cartilage disease,defects and injuries of the knee. Preferably, the device is portable andcan be programmed to deliver a wide variety of specific signals toregulate gene expression in a wide variety of selected diseases of themusculoskeletal system (bone, cartilage, tendon, and muscle), thecardiovascular system (angiogenesis, vascular repair,revascularization), skin and wound healing, and in preventing tumormetastases. The present invention is designed to meet these needs in theart.

SUMMARY OF THE INVENTION

The present invention meets the afore-mentioned needs in the art byproviding a non-invasive electromagnetic therapeutic method andapparatus for treating diseased and injured tissue in a human kneejoint. Such a method in accordance with the invention includes the stepof generating compound electric signals comprising a 60 kHz sine wavehaving a peak to peak voltage of approximately 4.6 V to 7.6 V and a 100%duty cycle signal that is generated for approximately 30 minutes and a50% duty cycle signal that is generated for approximately 1 hour afterthe 100% duty cycle signal. These signals selectively up-regulateAggrecan and Type II Collagen gene expression while selectivelydown-regulating metalloproteases. These compound electric signals arecommunicated to electrodes or coils in the proximity of a patient's kneefor the generation of a specific and selective electromagnetic fieldthat treats the diseased and/or injured tissue.

In accordance with the method of the invention, different duty cyclemodes may be selected for generation during a 24 hour time period. In afirst mode, the compound electric signal and 3 additional 50% duty cyclesignals are generated; in a second mode, the compound electric signaland 2 additional 50% duty cycle signals are generated; and in a thirdmode, the compound electric signal and 1 additional 50% duty cyclesignal is generated. Different voltage modes are selected in accordancewith a circumference of the patient's knee.

A device for generating specific and selective signals for applicationto electrodes for generating selective electric or electromagneticfields for the treatment of diseased tissue in a human knee joint inaccordance with the invention includes a signal generator that generatescompound electric signals that selectively up-regulates Aggrecan geneexpression and/or Type II Collagen gene expression and selectivelydown-regulates metalloprotease gene expression and other proteases inthe treatment of cancer and in the prevention of metastases of cancer,and an electric lead or a wireless connection that communicates thecompound electric signals to the electrodes or coils for fieldgeneration. The signal generator may include a switch that may bemanually or automatically switched to switch the signal generator intodifferent modes on different days. A microcontroller in the signalgenerator is responsive to time of day data to selectively generate thecompound electric signals at predetermined treatment times.

BRIEF DESCRIPTION OF DRAWINGS

The present invention will be better understood with reference to theaccompanying figures, of which:

FIG. 1 is a graphic representation of the response of MMP-1 mRNA geneexpression when articular cartilage chondocytes are exposed to a 20mV/cm capacitively coupled field for 30 minutes of 100% duty cycle inthe presence of interleukin (IL-1B). As indicated, the expression ofMMP-1 mRNA decreased dramatically by the end of 24 hours.

FIG. 2 is a graphic representation of the response of aggrecan mRNA geneexpression when articular cartilage condrocytes are exposed to a 20mV/cm capacitively coupled field of three different signal types in thepresence of IL-1B. As indicated, the expression of aggrecan mRNA isoptimal with one compound signal (30 minutes at 100% duty cycle followedimmediately by a 50% duty cycle for 1 hour) versus one simple signal (30minutes of 100% duty cycle) or the same simple signal repeated once.

FIG. 3 is a graphic representation of the response of Type II collagenmRNA gene expression when articular cartilage chondrocytes are exposedto a 20 mV/cm capacitively coupled field of three different signal typesin the presence of IL-1B. As indicated, the expression of Type IIcollagen mRNA is optimal with one compound signal (30 minutes 100% dutycycle followed immediately by a 50% duty cycle for 1 hour) versus onesimple signal (30 minutes of 100% duty cycle) or the same simple signalrepeated once.

FIG. 4 is a graphic representation of hexosamine production whenarticular cartilage chondrocytes are exposed to a 20 mV/cm capacitivelycoupled field of a compound signal (30 minutes of 100% duty cycle for 30minutes, followed immediately by a 50% duty cycle for 1) followed 4½hours later by a simple signal of 50% duty cycle for 1 hour, with orwithout the presence of IL-1B in the media. As indicated, the electricalstimulation produced a 1.6 field increase in hexosamine in the absenceof IL-1B and a 2.5 fold increase in hexosamine in the presence of IL-1B.

FIG. 5 is a graphic representation of hydroxyproline production whenarticular cartilage chondrocytes are exposed to a 20 mV/cm capacitivelycoupled field of a compound signal (30 minutes of 100% duty cyclefollowed immediately by a 50% duty cycle for 1 hour) followed 4½ hourslater by a simple signal of 50% duty cycle for 1 hour, with and withoutthe presence of IL-1B in the media. As indicated, the electricalstimulation produced a 1.7 fold increase in hydroxyproline in theabsence of IL-1B and a 3-fold increase hydroxyproline in the presence ofIL-1B.

FIG. 6 is a graphic representation of hexosamine production whenarticular cartilage chondrocytes are exposed to a capacitively coupledfield of various signal types. As indicated, a train of signals,consisting of a compound signal (30 minutes 100% duty cycle/1 hour 50%duty cycle) followed by 1 to 3 repetitions of a simple signal (each 1hour of 50% duty cycle) gives almost a 5 fold increase in hexosamineproduction but lesser increases in hexosamine production with signaltrains containing fewer repetitions of the simple signal (1 hour of 50%duty).

FIG. 7 is a graphic representation of hydroxyproline production whenarticular cartilage chondrocytes are exposed to a capacitively coupledfield of various signal types. As indicated, a train of signals,consisting of a compound signal (30 minutes 100% duty cycle/1 hour 50%duty cycle) followed by 1 to 3 repetitions of simple signals (each 1hour of 50% duty cycle) gives approximately a 2-fold increase inhydroxyproline production with one, two, or three repetitions of asimple signal.

FIG. 8 is a graphic representation of examples of various device signalmodes. As illustrated, each mode begins with a compound signal (30minutes 100% duty cycle/1 hour 50% duty cycle).

FIG. 9A is a pictorial representation of the human knee withself-adherent, flexible electrodes applied to the medial (inside) andlateral (outside) of the knee at the joint line for capacitive coupling;FIG. 9B is a pictorial representation of the lower torso with a fabricwrap or brace around the knees covering the electrodes or coils with apocket in the wrap or brace (Right) to hold the portable signalgenerator and a pocket worn on the belt (Left) to hold the power pack;and FIG. 9C is a pictorial representation of the human knee with afabric wrap or brace around the knees covering a coil for inductivecoupling.

FIG. 10 is a block diagram of the circuitry of the portable signalgenerator device of the invention, where basic signal and control flowsare indicated. Each block outlines specific circuits and theirfunctions. VCC=Voltage Controlled Circuit or regulated voltage source,CS=Current Sense circuit, and Op-Amp=Operational Amplifier or Outputdrive amplifier.

FIG. 11 is a schematic drawing of the circuit of FIG. 10.

DETAILED DESCRIPTION OF THE ILLUSTRATIVE EMBODIMENTS

The invention will be described in detail below with reference to FIGS.1-11. Those skilled in the art will appreciate that the descriptiongiven herein with respect to those figures is for exemplary purposesonly and is not intended in any way to limit the scope of the invention.All questions regarding the scope of the invention may be resolved byreferring to the appended claims.

Definitions:

As used herein, the phrase “signal” is used to refer to a variety ofsignals including mechanical signals, ultrasound signals,electromagnetic signals and electric signals output by a device.

As used herein, the term “field” refers to an electrical field withintargeted tissue, whether it is a combined field or a pulsedelectromagnetic field or generated by direct current, capacitivecoupling or inductive coupling.

Description of Illustrated Embodiments:

The invention is a portable device that enables the application ofcapacitive or inductively coupled electric fields to a patient's kneefor providing a desired therapeutic effect. The device provides a systemcoordinator with control of the stimulation signal to the subjectreceiving treatment. The system coordinator receives total control ofthe primary program download and subsequent upgrades to the programmingfor device modification and allows limited control ability to theinstaller of the device to set fitting and mode: A variety of powersources or a fixed power source may be used to power the device. Time,day and date information is used to set mode parameters for differenttreatments at different times of day or the week. Such information isalso useful in the storage and retrieval of dated records for historicalevaluation.

The device of the invention is designed to emit signals of variousdurations, amplitudes, frequencies, duty cycles, and waveforms invarious modes. The characteristics of the signals are selected toselectively up-regulate and down-regulate gene expressions as describedin detail in the afore-mentioned related applications. Such signals areconfigured as simple or compound. A simple signal is defined as onesignal of a given duration, amplitude, frequency, and duty cycle. Acompound signal is defined as two or more simple signals appliedsequentially, with or without an off break in between each simplesignal. The simple signal components of a compound signal may beidentical to each other or may vary one from another in duration,amplitude, frequency and/or duty cycle.

Several examples of such signals are shown in the figures to illustratehow various signal constructs can be designed in order to achievemaximum regulation of selected gene expressions. For example, whenarticular cartilage chondrocytes grown in micromass are exposed tointerleukin 1B (IL-1B), there is a dramatic increase in MMP-1 mRNA (asoccurs in osteoarthritis). However, as shown in FIG. 1, when acapacitively coupled electric field of 20 mV/cm (sine wave, 60 kHz) witha 100% duty cycle is applied for 30 minutes, the down-regulation ofMMP-1 mRNA is dramatic. Thus, only one 30 minute period of this specificsignal per 24 hours is optimal for maintaining the down-regulation ofMMP-1 mRNA and other proteases such as those used in the treatment ofcancer and in the prevention of metastases in cancer. For up-regulationof aggrecan mRNA, however, a compound signal of 30 minutes of a 100%duty cycle followed immediately by a 50% duty cycle for 1 hour in thepresence of IL-1B produces a 10-fold increase in aggrecan mRNA, as shownin FIG. 2. This compound signal is 5 fold more effective than are twosimple signals, each of 30 minutes duration and 100% duty cycle, whenthe signals are applied 4 hours apart. As shown in FIG. 3, the upregulation of Type II collagen mRNA follows the same pattern sinceaggrecan and Type II collagen gene expressions are complimentaryfunction-wise.

The effects of various combinations of simple and compound signals inincreasing the product of gene expressions, for example the increase inhexosamine production resulting from up-regulation of aggrecan mRNA andthe increase in hydroxyproline production resulting from up-regulationof Type II collagen mRNA, are illustrated in FIGS. 4 and 5. Thoseskilled in the art will appreciate that the initial compound signal(consisting of 30 minutes of 100% duty cycle followed by 1 hour of 50%duty cycle) down regulates MMP-1 mRNA (initial 30 minutes) andup-regulates aggrecan mRNA and Type II collagen mRNA (next one hour).Another 50% duty cycle signal is applied 4.5 hours later to furtherboost gene expression for aggrecan mRNA and Type II collagen mRNA. It isnot necessary to repeat the 30 minutes 100% duty cycle signal since thegene expression for MMP-1 is initially down regulated for a full 24hours. (FIG. 1). As shown in FIGS. 4 and 5, the application of thesignal constructs described above result in a 1.6 and 1.7 fold increasein the production of hexosamine and hydroxyproline, respectively, whenIL-1B is absent, and an even larger increase when IL-1B is present (2.5and 3 fold increase, respectively).

For even greater increases in hexosamine production a third signal of50% duty cycle boosts production 3.4 fold, and a fourth signal of 50%duty cycle boosts it to 4.8 fold per 24 hours (FIG. 6). Thus, a train ofsignals, the compound signal followed by three simple signals, providesmaximum hexosamine production per 24 hours using this construct. Asshown in FIG. 7, the same construct increases hydroxyproline productionto 1.9, 2.0, and 1.9 fold, respectively. Other constructs can easily bedevised by one knowledgeable in the field. For instance, an 8.3% dutycycle applied for 6 hours increases hyproxyproline by 5.1 fold. Thiscould be configured with a 50% duty cycle applied for 1 hour forhexosamine stimulation along with a 100% duty cycle for a 30 minutes todown-regulate MMP-1. These examples are given to show how different geneexpressions can be up-regulated and down-regulated in the same 24 hoursignal construct.

The device of the invention is designed to provide one or more modes,each applying various signal constructs. For example, as shown in FIG.8, one mode is designed to apply a compound signal followed by simplesignals 4.5 hours, 5 hours, and again 5 hours apart during a 24 hourcycle. Mode 2 is designed to apply an initial compound signal followedby two simple signals 4.5 and 9.5 hours later during a 24 hour cycle.Mode 3 is designed to apply a compound signal and a simple signal 4.5hours later during a 24 hour cycle. Thus, a patient may wear a deviceswitched to Mode 1 for use 24 hours a day, or switched to Mode 2 for useduring the daytime only, or switched to Mode 3 for use during the nightonly. It is obvious to anyone experienced in the field that the devicecan be configured to apply an electrical field of various wave forms,amplitudes, durations, frequencies, and duty cycles in various compoundand simple signal construct in one or various modes on different daysfor various periods of time.

As illustrated in FIG. 9A, the device of the invention may be connectedto two flexible, self adherent, conductive electrodes 10, 12 placed onthe skin on the medial (inside) and lateral (outside) of the knee at thejoint line. A short VELCRO™ wrap 14 or other material may be wrappedaround the electrodes 10, 12 to hold them in place, or the electrodes10, 12 may be fitted into a fabric knee wrap or brace 22 as shown inFIG. 9B such that the electrodes 10, 12 are a replaceable part of thewrap or brace 22 and are held in the wrap or brace 22 in such a way asto ensure good contact at the desired location on the inside and outsideof the knee at the level of the joint line.

The portable signal generator 18 of the invention is preferably small(approximately 3×2×½ inches), lightweight (6-8 oz), and powered by astandard battery (e.g., 9-volts). The device is portable and may be worneither attached to the knee wrap or brace 22 by a VELCRO™ strap 14 orfitted into a pouch 24 in the wrap or brace 22 with or without itsbattery pack, or the signal generator 18 may be worn at the belt line(waist) in pouch or holster 26 with or without (FIG. 9B) or above orbelow the knee by fitting into thigh or calf wraps secured by VELCRO™straps or snaps (not shown). The portable signal generator is connectedto each of the electrodes 10, 12 by one or more flexible leads 16,although a wireless connection (e.g., Bluetooth) may also be used.

The electrodes 10, 12 used in accordance with a capacitive couplingembodiment of the invention are flexible, non-metallic, approximately2×2 inches each in size, and are self-adherent. One electrode is worn onthe medial side of the knee and the other is worn on the lateral side ofthe knee as shown in FIG. 9A. As shown, both electrodes 10, 12 areplaced at the approximate level of the knee joint. The electrodes 10, 12are preferably disposable for replacement approximately every 5-7 days.The knee wrap or brace 22 either fits over the electrodes 10, 12 or thewrap or brace 22 contains a cut-out into which the electrodes 10, 12 canbe placed for proper spacing on each side (medial and lateral) of thejoint line.

In accordance with another implementation of the invention, theappropriate electric field can be delivered to diseased or traumatizedarticular cartilage using an inductive coupling device of the type shownin FIG. 9C. The electric field is generated in the knee by a coil 20containing N turns that is inserted into a knee wrap or brace 22 andslipped over the knee and centered thereon. A battery-powered supply ofcurrent is attached to the coil leads from the portable signal generatorsuch that a time varying current flows through the coil. This currentproduces a magnetic flux which in turn produces a time-varying electricfield. It is understood that the current amplitude, frequency, dutycycle and wave form(s) can be controlled from the power supply so as toproduce a therapeutic value for the E field.

As described in the aforementioned related application filed on Jun. 9,2003, the voltage output by the portable signal generator 18 forapplication to the electrodes 10, 12 or the inductive coupling coil 20is dependent upon the circumference of the patient's knee as follows:Switch Position Knee Circumference Voltage Output 1 Small (less than 15inches) 4.6 V p-p ± 10% 2 Medium (15-16 inches) 5.0 V p-p ± 10% 3 Large(16.1-18 inches) 5.6 V p-p ± 10% 4 Extra Large (Greater than 18 inches)7.6 V p-p ± 10%In other words, different voltage outputs are provided at differentswitch positions of the device based on the size of the patient's kneejoint. Current at the skin-electrode interface is set not to exceed 10mAmps.

The Signal Mode is selected as follows: Signal Mode Maximum TreatmentTime 1 24 hours/day 2 16 hours/day 3  8 hours/dayThus, a duty cycle/cycle time switch with 3 positions may be set inaccordance with the signaling mode (8, 16, or 24 hours).

Preferably, the patient does not have access to the switches for settingvoltage (based on knee size) and cycle time so that mode changes may bemade only by the treating physician or nurse.

Circuit Description:

FIG. 10 illustrates a circuit diagram of the portable electrotherapydevice 18 of the invention. As illustrated, the patient (User) andProgrammer's interface 105 is connected via a wired or wirelessconnection to a microcontroller 110 that downloads the operating system,source code, and application interface to display or retrieveinformation via a PC, laptop or PDA. The interface 105 also includes apower indicator (not shown) that lets the patient know that the device18 is operational. The microcontroller 110 coordinates the userinterface 105 with the rest of the circuit by executing stored programprocedures. The device 18 operates as an independent controller that isnot tethered to wires or display panels issuing control of the signaloutput according to date, day, and time of the operating program, asreceived from a clock calendar chip 120. The microcontroller 110 alsoretrieves data from the circuit such as current sense 190, power 140,150 and day, date, and time from the clock calendar chip 120 and storesthis data for later retrieval by the program coordinator (110, 105). Theclock calendar chip 120 is preferably powered by a separate battery andmaintains date, day, and time independently, thus allowing themicrocontroller 110 an external reference that is unaffected by power oruser interruption. The regulated switched voltage converter 130 acceptspower from a variety of battery voltages or from a fixed power source140 and supplies a regulated 5 volts (VCC) output 150 to power thedevice 18 and a switched 5 volt voltage output controlled by themicrocontroller 110 to be supplied to the switched voltage converter160. The switched voltage converter 160 takes a positive 5 volts in andcreates a negative 5 volts output to supply to the output driveamplifier 170. The drive amplifier 170 under control of themicrocontroller 110 supplies the output signal (4.6-7.6 voltspeak-to-peak at less than 10 mAmps as determined by the installer) tothe electrodes 10, 12 or the coil 20 via load stimulator 180.

The current is fed back in a feedback circuit (CS) 190, which senses theproper drain when the electrodes 10, 12 or coil 20 are positionedproperly to let the program coordinator (or installer) know whether thedevice 18 and electrodes 10, 12 or coil 20 are properly attached to thepatient for the period under evaluation. The load is the current drawthat is encountered when the electrodes 10, 12 or coil 20 are properlyplaced and current flows so as to generate an electric field.

The circuit schematic of the circuit of FIG. 10 is illustrated in FIG.11. Like elements are illustrated by like reference numerals. Interface105 of the device 18 includes the afore-mentioned switches for manuallyor automatically selecting the signal mode and the knee circumference.Preferably, these switches, whether manual or software implemented, mayonly be modified by the treating physician or nurse, thereby preventingthe patient from modifying the treatment regimen. The actual mode andknee circumference switching is accomplished within the microcontroller110. In one embodiment, the medical personnel or the patient may use aPC, PDA or other device to configure the device 18 via the interface 105and microcontroller 110 as desired for proper operation. The patientwill be able to determine that the power to the device 18 is ON if thepower indicator LED of interface 105 is lit.

Those skilled in the art will appreciate that the device of the presentinvention may be used to provide drive signals to electrodes in acapacitive coupling embodiment and to coils or a solenoid in aninductive coupling embodiment. The same or an additional mode switch maybe used to select between the capacitive and inductive couplingembodiments, with the respective drive signals provided accordingly.

Although implementations of the invention have been described in detailabove, those skilled in the art will readily appreciate that manyadditional modifications are possible without materially departing fromthe novel teachings and advantages of the invention. Any suchmodifications are intended to be included within the scope of theinvention as defined in the following claims.

1. A device for generating specific and selective signals for application to a capacitive coupling and/or inductive coupling device for the generation of selective electric or electromagnetic fields for the treatment of defective or diseased tissue in a human knee joint, comprising: a signal generator that generates compound electric signals that selectively up-regulate at least one of Aggrecan gene expression and Type II Collagen gene expression and selectively down-regulates metalloprotease gene expression; and means for communicating said compound electric signals to said capacitive and/or inductive coupling device.
 2. A device as in claim 1, wherein said compound electric signals comprise a 60 kHz sine wave having a peak to peak voltage of approximately 4.6 V to 7.6 V.
 3. A device as in claim 2, wherein said compound electric signals comprise a 100% duty cycle signal that is generated for approximately 30 minutes and a 50% duty cycle signal that is generated for approximately 1 hour after said 100% duty cycle signal.
 4. A device as in claim 3, wherein said signal generator further generates during a 24 hour time period at least one additional 50% duty cycle signal having a duration of approximately 1 hour.
 5. A device as in claim 4, wherein said signal generator is selectable into at least three modes, a first mode for generating during a 24 hour time period said compound electric signal and three of said additional 50% duty cycle signals, a second mode for generating during a 24 hour time period said compound electric signal and two of said additional 50% duty cycle signals, and a third mode for generating during a 24 hour time period said compound electric signal and one of said additional 50% duty cycle signals.
 6. A device as in claim 5, wherein said signal generator comprises a switch that may be manually or automatically switched to switch said signal generator into different modes.
 7. A device as in claim 1, further comprising means for holding said signal generator in proximity of a patient for communication with said capacitive and/or inductive coupling device.
 8. A device as in claim 7, wherein said holding means comprises a Velcro™ strap that holds said signal generator to one of a patient's leg and a knee wrap.
 9. A device as in claim 7, wherein said holding means comprises a pocket in one of a knee wrap and leg wrap.
 10. A device as in claim 7, wherein said holding means comprises one of a pocket and a holster worn at the patient's waist.
 11. A device as in claim 1, wherein said communicating means comprises one of an electric lead and a wireless connection.
 12. A device as in claim 1, wherein said signal generator comprises a microcontroller responsive to time of day data to selectively generate said compound electric signals at predetermined treatment times.
 13. A device as in claim 1, wherein said signal generator generates compound electric signals that down-regulate the gene expression of metalloproteases and other proteases in the treatment of cancer and in the prevention of metastases in cancer.
 14. A device as in claim 1, wherein said signal generator is selectable to generate said compound electric signal at different voltages in accordance with a circumference of a patient's knee.
 15. A non-invasive electromagnetic therapeutic method for treating defective or diseased tissue in a human knee joint, comprising the steps of: generating compound electric signals comprising a 60 kHz sine wave having a peak to peak voltage of approximately 4.6 V to 7.6 V and a 100% duty cycle signal that is generated for approximately 30 minutes and a 50% duty cycle signal that is generated for approximately 1 hour after said 100% duty cycle signal; and communicating said compound electric signals to one of a capacitive coupling and an inductive coupling device in the proximity of a patient's knee for the generation of a specific and selective electromagnetic field that treats said diseased tissue.
 16. A method as in claim 15, wherein said generating step comprises the step of generating during a 24 hour time period at least one additional 50% duty cycle signal having a duration of approximately 1 hour.
 17. A method as in claim 16, wherein said generating step comprises the step of selecting one of at least three duty cycle modes, a first mode for generating during a 24 hour time period said compound electric signal and three of said additional 50% duty cycle signals, a second mode for generating during a 24 hour time period said compound electric signal and two of said additional 50% duty cycle signals, and a third mode for generating during a 24 hour time period said compound electric signal and one of said additional 50% duty cycle signals.
 18. A method as in claim 15, comprising wherein said generating step comprises the step of selecting a voltage for said compound electric signal in accordance with a circumference of a patient's knee. 